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首页> 外文期刊>Cellular microbiology >ATP scavenging by the intracellular pathogen Porphyromonas gingivalis inhibits P2X(7)-mediated host-cell apoptosis
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ATP scavenging by the intracellular pathogen Porphyromonas gingivalis inhibits P2X(7)-mediated host-cell apoptosis

机译:细胞内病原体牙龈卟啉单胞菌清除ATP抑制P2X(7)介导的宿主细胞凋亡

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摘要

The purinergic receptor P2X(7) is involved in cell death, inhibition of intracellular infection and secretion of inflammatory cytokines. The role of the P2X(7) receptor in bacterial infection has been primarily established in macrophages. Here we show that primary gingival epithelial cells, an important component of the oral innate immune response, also express functional P2X(7) and are sensitive to ATP-induced apoptosis. Porphyromonas gingivalis, an intracellular bacterium and successful colonizer of oral tissues, can inhibit gingival epithelial cell apoptosis induced by ATP ligation of P2X(7) receptors. A P. gingivalis homologue of nucleoside diphosphate kinase (NDK), an ATP-consuming enzyme, is secreted extracellularly and is required for maximal suppression of apoptosis. An ndk-deficient mutant was unable to prevent ATP-induced host-cell death nor plasma membrane permeabilization in the epithelial cells. Treatment with purified recombinant NDK inhibited ATP-mediated host-cell plasma membrane permeabilization in a dose-dependent manner. Therefore, NDK promotes survival of host cells by hydrolysing extracellular ATP and preventing apoptosis-mediated through P2X(7).
机译:嘌呤能受体P2X(7)参与细胞死亡,抑制细胞内感染和炎症细胞因子的分泌。 P2X(7)受体在细菌感染中的作用已主要在巨噬细胞中确立。在这里,我们显示了原发性牙龈上皮细胞,口服先天免疫反应的重要组成部分,也表达功能性P2X(7),并且对ATP诱导的凋亡敏感。牙龈卟啉单胞菌(Porphyromonas gingivalis)是一种细胞内细菌,是口腔组织的成功定居者,可以抑制由P2X(7)受体的ATP连接诱导的牙龈上皮细胞凋亡。 ATP消耗酶核苷二磷酸激酶(NDK)的牙龈卟啉单胞菌同源物在细胞外分泌,是最大程度抑制细胞凋亡所必需的。 ndk缺陷型突变体无法阻止ATP诱导的宿主细胞死亡,也无法阻止上皮细胞的质膜透化。用纯化的重组NDK处理以剂量依赖性方式抑制ATP介导的宿主细胞质膜透化。因此,NDK通过水解细胞外ATP并阻止通过P2X介导的凋亡来促进宿主细胞的存活(7)。

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